BTG1: A triiodothyronine target involved in the myogenic influence of the hormone

The product of the B-cell translocation gene 1 (BTG1), a member of an antip roliferative protein family including Tis-21/PC3 and Tob, is thought to pla y an important role in the regulation of cell cycle progression. We have sh own in a previous work that triiodothyronine (T3) stimulates quail myoblast differentiation, partly through a cAMP-dependent mechanism involved in the stimulation of cell cycle withdrawal. Furthermore, we found that T3 or 8-B r-cAMP increases BTG1 nuclear accumulation in confluent myoblast cultures. In this study, we report that BTG1 is essentially expressed at cell conflue nce and in differentiated myotubes. Whereas neither T3 nor cAMP exerted a d irect transcriptional control upon BTG1 expression, we found that AP-1 acti vity, a crucial target involved in the triiodothyronine myogenic influence, repressed BTG1 expression, thus probably explaining the low BTG1 expressio n level in proliferating myoblasts. In transient transfection studies, we d emonstrated that an AP-l-like sequence located in the BTG1 promoter was inv olved in this negative regulation. Our present data also bring evidence tha t the stimulation of BTG1 nuclear accumulation by T3 or 8-Br-cAMP probably results from an increased nuclear import or retention in the nucleus. Lastl y, BTG1 overexpression in quail myoblasts mimicked the T3 or 8-Br-cAMP myog enic influence: (i) inhibition of myoblast proliferation due to an increase d rate of myoblast withdrawal from the cell cycle; and (ii) stimulation of terminal differentiation. These data suggest that BTG1;1 is probably involv ed in T3 and cAMP myogenic influences. In conclusion, BTG1 is a T3 target i nvolved in the regulation of myoblast differentiation. (C) 1999 Academic Pr ess.